title: Cudratricusxanthone G inhibits human colorectal carcinoma cell invasion by MMP-2 down-regulation through suppressing activator protein-1 activity.
abstract: Cudratricusxanthone G (CTXG), a natural bioactive cudratricusxanthone extracted from C. tricuspidata, has shown anti-cancer properties. However, the function and mechanism of CTXG in tumor invasion have not been elucidated to date. In this study, we investigated the inhibitory effect of CTXG on the proliferation, migration and invasion of SW620 cells. We found that MMP-2, a pivotal factor in tumor invasion, was suppressed in both expression and activation by CTXG in a dose-dependent manner. The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase. Furthermore, CTXG also inhibited the transcriptional activity of AP-1 (activator protein-1). In conclusion, our data demonstrate that CTXG exerted anti-invasion action in SW620 cells by targeting MMP-2 though regulating the activities of Rac1, Cdc42 and their downstream transcriptional factor AP-1. These results are the first to reveal the novel functions of CTXG in cancer cell invasion and its molecular basis for the anti-cancer action.
authors.affiliation: The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Kuang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Qufei
authors.initials: Q
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Du
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Aijun
authors.initials: A
authors.lastname: Hou
authors.forename: Min
authors.initials: M
authors.lastname: Qian
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D031624:Maclura; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014158:Transcription, Genetic; D044004:Xanthones / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D018808:Transcription Factor AP-1; D044004:Xanthones; C559148:cudratricusxanthone G; D020778:Matrix Metalloproteinase 2; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein